Xianlong Li1, Qian Zhang1, Rui Zhang2, Nan Cheng1, Na Guo1, Yiqian Liu3, Jun Cai4, Dongdong Yuan5. 1. Department of Anesthesiology, the Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road, Guangzhou, PR China. 2. Department of Anesthesiology, Zhongshan Ophthalmic Center of Sun Yat-sen University, Xian lie South Road, Guangzhou, PR China. 3. Southern Medical University, Sha Tai South Road, Guangzhou, PR China. 4. Department of Anesthesiology, the Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road, Guangzhou, PR China.. Electronic address: gzcaijun@hotmail.com. 5. Department of Anesthesiology, the Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road, Guangzhou, PR China.. Electronic address: yuandongdong123@126.com.
Abstract
INTRODUCTION: Pregnancy-induced hypertension (PIH) is the most common serious complication of pregnancy, resulting in significant maternal and fetal morbidity and mortality. Vasospasm is the main pathogenesis of PIH, which leads to the hemodynamic changes and the injury of vascular endothelial cells. However, the underlying mechanism is still unclear. Monocyte-endothelial adhesion is always considered to be one of the most important indicators of vascular endothelial cell injury. Connexin43 (Cx43) plays an important part in monocyte-endothelial adhesion. Thus, we explored effects of Cx43 on cell adhesion in PIH-induced vascular endothelial cells injury. METHODS: We obtained human umbilical vein endothelial cells (HUVECs) from patients with or without PIH. Different methods, such as inhibitors: oleamide and Gap26, or specific siRNA were used to alter Cx43 channels function or protein expression in normal or PIH-HUVECs. U937-HUVECs adhesion, adhesion molecules expression, such as VCAM-1 and ICAM-1, and the activity of PI3K/AKT/NF-κB signaling pathway were determined. RESULTS: Monocyte-endothelial adhesion on PIH-HUVECs was much more obvious than that on normal HUVECs. Inhibition of Cx43 protein expression could attenuate cell adhesion significantly, however, function of Cx43 channels had no effects on it. Alternation of Cx43 protein expression on PIH-HUVECs mediated VCAM-1 and ICAM-1 expression via regulating the activity of PI3K/AKT/NF-κB signaling pathway. CONCLUSIONS: We firstly reported Cx43 protein expression on PIH-HUVECs was much higher than that on normal HUVECs. Elevation of Cx43 protein expression within the vasculature resulted in PI3K/AKT/NF-κB signaling pathway activation and VCAM-1 and ICAM-1 over-expression, which ultimately lead to monocyte-endothelial adhesion increase.
INTRODUCTION: Pregnancy-induced hypertension (PIH) is the most common serious complication of pregnancy, resulting in significant maternal and fetal morbidity and mortality. Vasospasm is the main pathogenesis of PIH, which leads to the hemodynamic changes and the injury of vascular endothelial cells. However, the underlying mechanism is still unclear. Monocyte-endothelial adhesion is always considered to be one of the most important indicators of vascular endothelial cell injury. Connexin43 (Cx43) plays an important part in monocyte-endothelial adhesion. Thus, we explored effects of Cx43 on cell adhesion in PIH-induced vascular endothelial cells injury. METHODS: We obtained human umbilical vein endothelial cells (HUVECs) from patients with or without PIH. Different methods, such as inhibitors: oleamide and Gap26, or specific siRNA were used to alter Cx43 channels function or protein expression in normal or PIH-HUVECs. U937-HUVECs adhesion, adhesion molecules expression, such as VCAM-1 and ICAM-1, and the activity of PI3K/AKT/NF-κB signaling pathway were determined. RESULTS: Monocyte-endothelial adhesion on PIH-HUVECs was much more obvious than that on normal HUVECs. Inhibition of Cx43 protein expression could attenuate cell adhesion significantly, however, function of Cx43 channels had no effects on it. Alternation of Cx43 protein expression on PIH-HUVECs mediated VCAM-1 and ICAM-1 expression via regulating the activity of PI3K/AKT/NF-κB signaling pathway. CONCLUSIONS: We firstly reported Cx43 protein expression on PIH-HUVECs was much higher than that on normal HUVECs. Elevation of Cx43 protein expression within the vasculature resulted in PI3K/AKT/NF-κB signaling pathway activation and VCAM-1 and ICAM-1 over-expression, which ultimately lead to monocyte-endothelial adhesion increase.
Authors: Jinhui Chen; Gang Liu; Yan Hong; Jing Han; Zhe Yang; Yanping Yang; Hong Li; Shumin Wang; Lili Jue; Qi Wang Journal: Biomed Res Int Date: 2022-09-15 Impact factor: 3.246